Insulin-blood cardioplegia decreases matrix metalloproteinase activity in ischaemia-reperfusion injury during coronary artery bypass surgery

Reperfusion of myocardium during coronary bypass activates matrix metalloproteinases (MMPs) with changes occurring in the levels of tissue inhibitors of metalloproteinases (TIMPs) in the myocardium. This study investigated the effects of insulin-blood cardioplegia on MMP activity and TIMP levels during reperfusion. Non-diabetic patients undergoing coronary artery bypass graft with cardiopulmonary bypass were randomized into a control group (n = 12) or an insulin group (n = 12). Blood cardioplegia was used for both groups; insulin and glucose were added to the insulin group. Blood samples were obtained from the coronary sinus just before aortic cross clamping and after 1 and 30 min of reperfusion. Plasma proenzyme MMPs (proMMP-2 and -9) and TIMPs (TIMP-1 and TIMP-2) levels were measured. There were no differences between groups for MMP-2 and TIMP-2 levels. However, insulin diminished proMMP-9 activation, although some still occurred. TIMP-1 consumption lessened during reperfusion which, we conclude, was as a result of the diminished MMP activation. This is the first open heart surgery study in which diminished MMP activation was achieved via a metabolic change